Friedreich's Ataxia (FRDA) is a rare but serious degenerative neuromuscular disease resulting from diminished levels of the mitochondrial protein Frataxin (FXN) (reviewed by Schmucker and Puccio, Human Molecular Genetics, 2010 Apr. 15; 19(R1): R103-110; Pandolfo and Pastore, J. Neurol, 2009, 256 (Suppl. 1), 9-17). The function of FXN is not entirely clear, but it seems to be involved in assembly of iron-sulfur clusters. It has been proposed to act as either an iron chaperone or an iron storage protein. In many cases, FRDA is caused by a large expansion of a GAA triplet-repeat sequence in the first intron of the frataxin gene, which can lead to decreased transcription of full-length transcripts (P. Patel and G. Isaya, Am. J. Hum. Genet. 69:15-24 (2001)). As a result, FRDA patients suffer progressive iron accumulation and dysfunction in mitochondria (O. Gakh, et al., Biochemistry, 41:6798-6804 (2002)), resulting in symptoms that may include mild to severe muscular impairments, including ataxia, fatigue, muscle loss, blurring of vision, and slurring of speech. In addition, FRDA patients may develop severe and life threatening cardiomyopathies and are susceptible to motorneuron dysfunction and FRDA-associated diabetes mellitus. Symptoms typically begin sometime between the ages of 5 to 15 years, but in Late Onset, FRDA may occur in the 20 s or 30 s. Patients with FRDA typically die by the 4th or 5th decade of life.
Currently, there is no approved therapy for treatment of FRDA.